Background and Objective
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is characterized by cerebral vascular dysfunction, with hypoperfusion likely causing strokes and dementia. CADASIL exhibits significant phenotypic variability both within families and across different cohorts, necessitating an objective surrogate marker for CADASIL.
Methods
In this single-center prospective study, genetically confirmed CADASIL patients received the Montreal Cognitive Assessment (MoCA), MRI, and SPECT scans after providing written informed consent. We examined the association of cognitive impairment, defined as a MoCA score less than 26, with cerebral blood flow in the frontal lobe measured by arterial spin labeling (ASL-CBF), and with the volumes of white matter hyperintensities on FLAIR images (WMH). Additionally, CBF in the precentral area was measured by SPECT (SPECT-CBF). MoCA, MRI and SPECT were conducted within two months.
Results
Between November 2021 and October 2022, 46 (18 female) CADASIL patients were enrolled (median [interquartile range]: age, 53 [49-57] years; MoCA scores: 25 [22-27]; ASL-CBF, 26.3 [20.3-33.9] ml/100g/min; WMH volume, 44.1 [30.1-61.8] ml; SPECT-CBF, 43.5 [42.1-47.2] ml/100g/min). The NOTCH3 gene p.R75P mutation was the most prevalent (n=10). In the logistic regression analysis for cognitive impairment, we observed a strong association with ASL-CBF (odds ratio [95% CI]: 0.827 [0.738-0.927], p=0.001), but not with WMH volumes (1.023 [0.933-1.054], p=0.141) or SPECT-CBF (0.919 [0.805-1.049], p=0.209).
Conclusion
This study demonstrated that ASL-CBF was strongly associated with cognitive function in patients with CADASIL. ASL may be the optimal imaging biomarker for monitoring cognitive impairment in small vessel diseases.